Diabetes History 3: The Rise of Insulin

You've returned! Welcome back to the nail-biting conclusion of diabetes history. When I say "history," I'm talking a hundred years ago or more. "History" could also include more recent events, like synthetic insulins, the failed attempt at an insulin nasal spray, and the grotesque price gouging pharmaceutical companies engage in with life-sustaining medicine. But I'm writing about The Dark Times, when a diagnosis of diabetes meant death.

Y'know... the good times! 😁

We've reached the miracle for which all diabetics were waiting. I’m not religious. I have continuously stated that if I could just have the mailing address and phone number of whatever divine being that made the universe, I’d be a lot better with the whole "faith thing." However, not all miracles need be a parting of the seas, a pillar of fire, or the killing of the first born of one’s enemies. Sometimes miracles are a series of unusual twists of fate.

I mentioned the births of Frederick Banting and Charles Best in my last post, but said nothing else about them. That’s because up until this moment in the timeline, there was nothing else to say. Now I need to backtrack a bit to say more about Dr. Banting and his lab assistant. These two men, specifically Dr. Frederick Banting, are what constitute a miracle for me and all diabetics. His life could have, and should have, taken him down a very different path. Instead, there will be several twists along his life’s course that are what I consider miraculous. I'll even enumerate them. Just... don’t let my calling them Fred or Chuck seem irreverent; I have nothing but the greatest respect for these men.

Oh... for you kids out there, your hashtag symbol was once called the pound sign and substituted the word "number."

Twist #1: Once Fred was done with public education, he attempted to join the Canadian army. Thankfully, they rejected him because of his poor eyesight. I’m sure there were plenty of soldiers in the field with corrective lenses, so... I don’t know. Maybe his weren’t stylish enough for the Canadian Army? Your guess is as good as mine.

Twist #2: At the urging of his devout Methodist parents, the then Mr. Banting entered into the University of Toronto to study divinity with the goal of becoming a priest. Luckily for diabetics around the globe, he didn’t hear the calling and transferred out of his religious studies to tackle medicine.

Twist #3: File this one under Just Damned Lucky: Fred Banting joined the Canadian Army Medical Corps because World War I created a need for army medics. He, himself, was wounded at the Battle of Cambrai. Despite his injury, he aided other wounded men for up to 16 hours before another doctor forced him to rest. His actions won him one of the 2,877 Military Crosses that were given for heroism under fire (out of the 150,000 nominations). Considering the lack of medical technology and the less-than-sterile conditions on the battlefield, I consider it “providence” that his wound and lack of care for numerous hours didn’t cripple or kill him.

Twist #4: After the war, Banting, as I understand it, became... something. There seems to be a jumble of information that occurs between 1920 and 1922. One source said he was a surgeon. Another said he was also a lecturer at the University of Western Ontario on the subjects of pharmacology and anthropology. Yet another says he didn’t earn his M.D. until 1922, which leaves me to wonder how he was permitted to practice medicine at all up until then! I dunno... Maybe the requirements to be called "doctor" were a lot less stringent than they are today.

Twist #5: While Banting was either doing one thing or many things during those years, he eventually sat down to read The Relation of the Islets of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis by Moses Barron. Not only a title that just rolls off the tongue, but had to be a real page turner! (If you think I was able to read and understand it, you got another think coming.) This medical treatise gave Dr. Banting an idea, so he went to his boss, Dr. J. J. R. Macleod, and requested the resources to pursue it.

Twist #6: Research resources were tight. Macleod said that Fred could have 10 dogs and one assistant. At the time, Banting had two assistants available to him, both medical students. So how did he choose between the two? A coin toss. I’m not even kidding. The winner was Charles Herbert Best.

The dynamic duo of Banting and Best went to work, and while I could go into details of that work, I won’t. It’s the animal lover in me that makes me refrain from discussing what was done to those 10 dogs, some of the best boys and girls ever! Besides, what matters are the results. They were able to extract insulin from the islets of Langerhans of the dogs’ pancreases. Their extract was then refined by Dr. James Collip.

On 23 January 1922, 14-year-old Leonard Thompson became the very first diabetic to receive a dose of insulin. Thanks to the starvation diet, Leonard weighed all of 66 pounds at the time. From then on, diabetes would no longer be a death sentence. Instead, it would be a disease that could either be merely troublesome or extremely serious... but very few people would ever die from diabetes again. In fact, Mr. Thompson died 13 years later from pneumonia, not diabetes!

That sounds weird, right? “Very few people would ever die from diabetes again.” It’s true, and I’ll try to explain it later, but people rarely die directly from diabetes!

Our hero, Dr. Frederick Banting,

seen here wearing the glasses that

kept him out of the Canadian Army.

In October of 1923, Banting and Macleod received the Nobel Prize in Physiology or Medicine. Dr. Banting initially declined the award, feeling that Charles Best should have been named as well in the achievement. In fact, he insisted that Best’s work was pivotal to their overall accomplishments. In the end, Banting shared the monetary award with Best, while Macleod shared his award with Collip.

Dr. Banting was knighted in 1934, becoming Sir Fredrick Banting. Or was it Sir Dr. Frederick Banting? Dr. Sir Frederick Banting? Dr. Frederick Sir Banting? One of those, I'm sure.

He was killed in a plane crash on February 21, 1941.

The fates and fortunes of the other doctors are yours to research if you'd like. Fred was the idea man who got the ball rolling on finding a medication to treat diabetes. We are alive today because of him! That's not hyperbole. It's a fact.

And so we come to the end of our journey through the annals of diabetes history. Join me for my next post, where I explore why diabetics were forced to wear roller skates and listen to disco throughout the 70's.

They weren't. I'm just in a weird mood as I type this. 😉

Laughing historically at doctors

Welcome back, sugar bear! Crap. You could be a diabetic like me. Ummm... Sugar-free bear? Maybe?! Y'know, maybe pet names aren't something I should try. That, or lean into them WAY too hard to offset the awkwardness. I dunno. Could be fun.

Anyway, I was covering the history of diabetes, which I'm sure you'll all agree is some edge-of-your-seat, steal-your-breath-away material. However, history helps us put the present into perspective. Think for a moment about what was and what is. Last post I said, "Those who were diagnosed with diabetes ... were almost immediately written off as terminal." I was diagnosed when I was seven. Given a proper diabetic starvation diet, I could have lived to the ripe old age of 12... if I was lucky.

That said, let's get into it with the subject of... Oh, look. The aforementioned starvation diets!

During the Franco-Prussian War, which was between 19 July 1870 to 10 May 1871, another French physician, Apollinaire Bouchardat, noticed a decrease of glycosuria, (sweet urine), in diabetic patients when food was being rationed in Paris. It’s at this point that the concept of a diet for diabetics was born, and not the idea of simply eating any one food item as treatment. So you can blame him for why cake and candy have been removed from our menus. Catoni, a diabetes specialist of Italian decent, would actually go as far as to place his patients under lock and key to enforce their diets. (Other inmates: "What you in for, man?" Diabetic: "First degree polyuria and polydipsia, and second degree glycosuria.") 

While studying for his doctorate at the Berlin Pathological Institute in 1869, Paul Langerhans isolated regions of the pancreas composed of cells that did... something. No, he didn’t know exactly what their functions were, but he’d narrowed them down, and they would eventually play an important role in diabetes treatment. They’re called - surprise, surprise - the islets of Langerhans. When and if I get around to discussing the function of the pancreas in relation to diabetes, the islets of Langerhans will be important. So write that down.

Why aren't you writing that down? Don't tell me you are; I can see you're not! I'll bet you haven't been taking any notes at all. What's polyuria? I see you opening up Google!

Okay, I'll stop.

Twenty years after Langerhans, Oskar Minkowski and Josef von Mering, while working at the University of Strasbourg, Austria, induced diabetes in dogs by removing their pancreas. Mind you, I’m no fan of vivisection, (experimentation on animals), but when it affects my life directly, I manage to tolerate such things. It was this study that isolated the pancreas as the gland responsible for glucose control within the body.

Now here are a pair of red-letter dates in diabetes history: 14 November 1891 and 28 February 1899. Those are the days that Frederick Banting and Charles Best were born respectively. You may not care all that much about them right now, but if you're a diabetic, you will! But more about them later.

The start of the 20th century saw many “fad” diets being used to treat diabetes. All probably saw to the deaths of numerous patients, as well. The “oat cure,” the “rice cure,” and “potato therapy” were all rich with carbohydrates, which the patients couldn’t process properly to start with. (Fear not, my information-hungry friend. I will get to "What is diabetes?" eventually.) And since opium was seen as a virtual panacea (cure-all) at the time, it was also used in the treatment of diabetes. That last probably had diabetics skipping along, singing, “I’m gonna die and I don’t care.” The only thing I can say in a positive manner about using opiates to treat diabetes is that the diabetics probably suffered a lot less pain.

NOTE: Opioids are their very own can of worms that I may or may not open later. But I will state this much: they are NOT an answer; they are a stop-gap.

Between the years of 1910 and 1920, Frederick Madison Allen and Elliot P. Joslin became the leading diabetes experts in the United States. Oh... and in 1910, saccharin becomes available. Just thought you’d want to know that coffee could be safely sweetened for diabetics once more, as they had in days of old.

Dr. Allen was the first to truly develop a diet that would prolong the lives of diabetics. His “starvation diet” focused on a severe reduction of carbohydrates. This didn’t change the overall fact that diabetes mellitus was a terminal illness, but it gave them a few extra years. As a side note, in almost everything I've read while researching the history of diabetes, there is mention that he also opened the Physiatric Institute, (not psychiatric), in Morristown, New Jersey, which was the first clinic solely dedicated to those diagnosed with diabetes mellitus.

To be clear, and to demonstrate how well we diabetics have it today, allow me to explain how the starvation diet worked. This data comes from a New York Times article that was published 13 February 1916. (Because I'm using old notes, I don't know if this is a direct quote.) "The patient would begin with a period of fasting for eight to 10 days. Coffee, tea, water, and very small amounts of fruit were permitted. This was done in an effort to come as close to the elimination of sugar as possible in patients. Following that, diabetic patients were given an incredibly strict diet to follow. Should their glucose levels start to rise abnormally once more, they would repeat the process all over again, starting with the fasting."

Sounds like a real treat, doesn't it?

Dr. Joslin’s work essentially confirmed the findings of Dr. Allen, but he was more of a mind that what should be reduced in the diabetic’s diet was fat. Who would have guessed that both were correct, and that limiting both would help maintain control of diabetes? Dr. Joslin was also an advocate of educating patients to care for themselves. In 1956, his practice was moved to One Joslin Place in Boston, MA, where it would become, and remain, the largest facility dedicated to the care and education of diabetics.

I would, however, like to note something that Dr. Joslin said. Despite all of his great work as a “diabetologist,” there is a quote from him that I find staggeringly dumb. He claimed diabetes mellitus was “the best of the chronic diseases” because it was “clean, seldom unsightly, not contagious, often painless and susceptible to treatment.” This may have been a perfectly justifiable statement from his observations, and he was, after all, a diabetes expert... but until he could experience the effects of the illness on himself, I personally think he should have said no such thing. “Clean.” Was putting out urine lousy with sugar a neat process? “Seldom unsightly.” Patients emaciated by the dehydration process were looking good to him, were they? “Not contagious.” Well, he couldn't be 100% wrong, but then a broken clock is right at least twice a day. “Often painless.” The description given by Aretaeus didn’t sound all that painless to me, with patients literally dying of what seemed to be an unquenchable thirst. “Susceptible to treatment.” Diet was all they had in 1920. Until the era of “Joslin and Allen,” only a German doctor, Georg Ludwig Zueler, had come close to a medicinal treatment, injecting a comatose patient with a pancreatic extract called “Acomatrol.” There were severe side effects, (the actual side effects remain unknown and immune to a Google search), and the patient died when the supply of the drug was exhausted.

I'm going to stop here to allow you to absorb some of the medieval things diabetics had to endure in the past. Try - TRY - to put yourself in their shoes. "The oat cure"?!? "The rice cure"?!? "Potato therapy"?!? Look, I don't know about you, but my body metabolizes potatoes into glucose at an astounding rate! Imagine if all they still had were their absurd guesses. "Well, the commercial says that Snickers really satisfies. Have we tried 'the Snickers' diet yet?" But fear not! Banting, Best, Macleod, and Collip are up next, so brace yourself for some hot chemical and hormonal history!

Getting completely historical

I know what you're thinking. Rob, you mentioned the history of diabetes in your first post. Is there really all that much history? Well, dear reader, there's at least enough for a blog post or two. 😉

The first documentation of diabetes was made in 1552 B.C. A piece of papyrus from the 3rd Egyptian Dynasty, written by a physician named Hesy-Ra, mentions the symptom of polyuria, AKA frequent urination. (You might want to remember that one, as polyuria plays a major role in the life of a diabetic.) The cause of the illness was unknown, but that didn’t stop Hesy-Ra from attempting treatment. He prescribed a special diet of fruits, grains, and honey. The patients probably died shortly thereafter because there was so much sugar in their blood that it flowed like tree sap. And while I'm making a joke about his treatment, my reading indicates that this diet actually helped, although I have absolutely NO idea how. It's completely counterproductive to what I know about diabetes. That many carbs and sugars should have had diabetics dying by the cartload.

In or around 1500 B.C., healers began to notice that ants were attracted to the urine of those who were diagnosed with diabetes. With our current knowledge, we understand this as the ants being attracted to the excessive sugar in the liquid waste.

The next time diabetes received any recognition was in or around 150 A.D. A Greek physician, Aretaeus of Cappadocia, inappropriately described the disease as the melting of the body into urine. His notes, translated by Francis Adams in 1856, say the following.  “Diabetes is a dreadful affliction, not very frequent among men, being a melting down of the flesh and limbs into urine. The patients never stop making water and the flow is incessant, like the opening of the aqueducts. Life is short, unpleasant and painful, thirst unquenchable, drinking excessive and disproportionate to the large quantity of urine, for yet more urine is passed. If for a while they abstain from drinking, their mouths become parched and their bodies dry; the viscera seem scorched up, the patients are affected by nausea, restlessness and a burning thirst, and within a short time they expire.” ("Making water," by the way, was their way of saying "peeing.") Factually, in terms of the flesh and limbs melting down into urine, he was completely off the mark, but it’s not as though he had an electron microscope with which to study slides of urine samples. If he did, he would have noted a distinct lack of material that was the patient's supposedly “melting body.” Still, Aretaeus was accurate in his description of the symptoms. Because it seemed as though the human body was acting as a siphon, he gave the disease the first part of its name, “diabetes.” 

NOTE: There is conflicting information on this, but I only found one note giving credit to Apollonius of Memphis, Egypt, in the naming of the disease in 250 B.C. All others seem to credit Aretaeus.

Yet another error in diagnosis occurred in 164 A.D., when another Greek, Galen of Pergamum, mistakenly diagnosed diabetes as a disease of the kidneys. As per what translation I could find, “Diabetes is a genuine kidney disease, analogous to voracious appetite.” Let's face it. It was the most logical guess to be made, since polyuria is THE big symptom of diabetes. SPOLIER WARNING: I know you want to wait to see how it ends on your own, but it turns out diabetes is a pancreatic illness. (Yeah, I'm sure I ruined the whole story.)

Assuming the wrong organ was behind the illness is only one of many wrong, unusual, or downright weird ideas pertaining to diabetes mellitus. Try this one on for size: To relieve the problem of frequent urination, it was suggested around 1000 A.D. that patients take up horseback riding. I... I just... I mean... Just imagine your bladder nearly full to bursting and some lunatic suggests you go bouncing around on the back of a horse! I can't find anything about the success of this "treatment," but I'm going to assume there were a lot of pee-covered horses.

There seems to be some confusion as to exactly when “mellitus,” the Ancient Greek word for “honey,” was added to the disease’s name. Some sources say it occurred as early as the 11th century, while others specifically credit Thomas Willis for it in 1675. A number of my sources said outright, “We don’t really know who added it.” This reference to honey was because those with diabetes had very sweet urine. If you’re anything like me, you have to wonder how anyone would even know that. Well, one of the ways to test for diabetes was to have a “water tester” come in and give the urine a taste. (And you thought your job sucked!) As disgusting as this may seem, urine is sterile when it leaves the body... for the most part. Okay, not always, but... We're getting off track! 

Those who were diagnosed with diabetes, “sweet urine,” “honey urine,” or one of several other monikers it carried at the time, were almost immediately written off as terminal. Their deaths would be excruciating, but relatively short. 

And if you really must know in order to shake off the idea of "water testers," Francis Home of Edinburgh in the U.K. developed a chemical test to measure sugar in urine in the 19th century.

In 1685, the sloppy work of Swiss doctor Johann Conrad Brunner dictated that the pancreas wasn’t essential to live. Ooooops! What he had done was extract the pancreases of dogs, and then sat back to see what happened. His initial expectations were that the dogs would die. Instead, they experienced polydipsia (excessive thirst) and polyuria, but these symptoms later regressed. Because the animals lived, he made his medical declaration that the pancreas wasn’t all that important.

BIG goof! His error was uncovered 200 years later, when it was found that the smallest remnants of pancreatic tissue would suffice to provide the body with insulin. Dr. Brunner failed to remove every remnant of the organ, thereby skewing his results.

Then came the brilliance of French physician, Priorry, in the late 1850's. For the life of me, I can’t find the reason why, but he advised his diabetic patients to intake copious amounts of sugar as a treatment. I can only imagine that his medical practice took a serious dive, as he didn’t have many living patients to pay their bills after such a recommendation. It was reported he had to get a newspaper route to help pay for his medical malpractice insurance.

Okay, that last sentence may not be factual. 😜 

There's more to the story, but I'm guessing this post is long enough. You may not get this one right now, but I assure you that the Banting and the Best is yet to come!